Paraptosis Inducer to Effectively Trigger Immunogenic Cell Death for Metastatic Tumor Immunotherapy with IDO Inhibition.

Paraptosis is characterized by the extensive vacuolization of endoplasmic reticulum (ER) and mitochondria, which will cause the release of damage-associated molecular patterns to promote immunogenic cell death (ICD). However, the tumor can develop an immunosuppressive microenvironment to affect the ICD activation for the purpose of immune escape. Herein, a paraptosis inducer (CMN) is constructed to amplify the ICD effect for efficient immunotherapy by inhibiting the activity of indoleamine 2,3-dioxygenase (IDO).

Coordination-Driven Self-Assembly of Biomedicine to Enhance Photodynamic Therapy by Inhibiting Proteasome and Bcl-2.

Tumor cells resist oxidative damage and apoptosis by activating defense mechanisms. Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Interestingly, BTZ can be coordinated with Sab to promote the assembly of uniform ternary biomedicine through non-covalent intermolecular interactions.

Cascade Immune Activation of Self-Delivery Biomedicine for Photodynamic Immunotherapy Against Metastatic Tumor.

Photodynamic therapy (PDT) can generate reactive oxygen species (ROS) to cause cell apoptosis and induce immunogenic cell death (ICD) to activate immune response, becoming a promising antitumor modality. However, the overexpressions of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1) on tumor cells would reduce cytotoxic T cells infiltration and inhibit the immune activation. In this paper, a simple but effective nanosystem is developed to solve these issues for enhanced photodynamic immunotherapy.